Because of the recent advances in embryo modeling techniques, and at the request of the Office of Science Policy in the Office of the Director at the National Institutes of Health, the National Academies of Sciences, Engineering, hosted a 1-day public workshop that would explore the state of the science of mammalian embryo model systems. The workshop, which took place on January 17, 2020, featured a combination of presentations, panels, and general discussions, during which panelists and participants offered a broad range of perspectives. Participants considered whether embryo model systems - especially those that use nonhuman primate cells - can be used to predict the function of systems made with human cells. Presentations provided an overview of the current state of the science of in vitro development of human trophoblast. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Mammalian Embryo Research and Pluripotent Stem Cells 3 Examining the Development of Extraembryonic Lineages 4 Stem CellBased Models of Human Embryos 5 Comparative Embryonic Development Across Species 6 Exploring Opportunities and Challenges with Mammalian Embryo Model Systems References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Consumer genomics, encompassing both direct-to-consumer applications (i.e., genetic testing that is accessed by a consumer directly from a commercial company apart from a health care provider) and consumer-driven genetic testing (i.e., genetic testing ordered by a health care provider in response to an informed patient request), has evolved considerably over the past decade, moving from more personal utility-focused applications outside of traditional health care to interfacing with clinical care in nontraditional ways. As consumer genomics has increasingly intersected with clinical applications, discussions have arisen around the need to demonstrate clinical and analytical validity and clinical utility due to the potential for misinterpretation by consumers. Clinical readiness and interest for this information have presented educational and training challenges for providers. At the same time, consumer genomics has emerged as a potentially innovative mechanism for thinking about health literacy and engaging participants in their health and health care. To explore the current landscape of consumer genomics and the implications for how genetic test information is used or may be used in research and clinical care, the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine hosted a public workshop on October 29, 2019, in Washington, DC. Discussions included such topics as the diversity of participant populations, the impact of consumer genomics on health literacy and engagement, knowledge gaps related to the use of consumer genomics in clinical care, and regulatory and health policy issues such as data privacy and security. A broad array of stakeholders took part in the workshop, including genomics and consumer genomics experts, epidemiologists, health disparities researchers, clinicians, users of consumer genomics research applications, representatives from patient advocacy groups, payers, bioethicists, regulators, and policy makers. This publication summarizes the presentations and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Workshop Overview 2 Understanding Consumer Genomics Use 3 Exploring the Role of Diversity and Health Disparities in Consumer Genomics 4 Integration Within Scientific and Medical Communities 5 Regulatory and Health Policy Issues 6 How Can Consumer Genomics Be Better Integrated to Improve Health? References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Each year, the individuals and organizations in the U.S. organ donation, procurement, allocation, and distribution system work together to provide transplants to many thousands of people, but thousands more die before getting a transplant due to the ongoing shortage of deceased donor organs and inequitable access to transplant waiting lists. Realizing the Promise of Equity in the Organ Transplantation System, a new consensus study report from the National Academies of Sciences, Engineering, and Medicine?s Committee on A Fairer and More Equitable, Cost-Effective, and Transparent System of Donor Organ Procurement, Allocation, and Distribution, provides expert recommendations to improve fairness, equity, transparency, and cost-effectiveness in the donor organ system. Table of Contents Front Matter Summary 1 Introduction and Study Context 2 The U.S. Organ Transplantation System and Opportunities for Improvement 3 Foundations for a Trustworthy Deceased Donor Organ Transplantation System 4 Confronting and Eliminating Inequities in the Organ Transplantation System 5 Saving More Lives and Enhancing Equity with Deceased Donor Organ Allocation Policies 6 Improving Procurement, Acceptance, and Use of Deceased Donor Organs 7 Measuring and Improving System Performance Appendix A: Public Meeting Agendas Appendix B: IOM and National Academies Solid Organ Transplantation Reports Appendix C: Biographical Sketches of Committee Members and Staff

The emerging multidisciplinary field of regenerative engineering is devoted to the repair, regeneration, and replacement of damaged tissues or organs in the body. To accomplish this it uses a combination of principles and technologies from disciplines such as advanced materials science, developmental and stem cell biology, immunology, physics, and clinical translation. The term "regenerative engineering" reflects a new understanding of the use of tissue engineering for regeneration and also the growing number of research and product development efforts that incorporate elements from a variety of fields. Because regenerative engineered therapies rely on live cells and scaffolds, there are inherent challenges in quality control arising from variability in source and final products. Furthermore, each patient recipient, tissue donor, and product application is unique, meaning that the field faces complexities in the development of safe and effective new products and therapies which are not faced by developers of more conventional therapies. Understanding the many sources of variability can help reduce this variability and ensure consistent results. The Forum on Regenerative Medicine hosted a public workshop on October 18, 2018, in Washington, DC, to explore the various factors that must be taken into account in order to develop successful regenerative engineering products. Invited speakers and participants discussed factors and sources of variability in the development and clinical application of regenerative engineering products, characteristics of high-quality products, and how different clinical needs, models, and contexts can inform the development of a product to improve patient outcomes. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Sources of Variability Associated with Regenerative Therapies: Lessons from Case Studies 3 Factors Contributing to Patient Variability 4 Addressing Variability in Donor Tissues and Cells 5 Addressing Variability and Meeting Quality Expectations in the Manufacturing Setting 6 Exploring Variability and Its Impact on Product Regulation and Outcomes 7 Potential Next Steps to Consider for Addressing Variability References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Genomic applications are being integrated into a broad range of clinical and research activities at health care systems across the United States. This trend can be attributed to a variety of factors, including the declining cost of genome sequencing and the potential for improving health outcomes and cutting the costs of care. The goals of these genomics-based programs may be to identify individuals with clinically actionable variants as a way of preventing disease, providing diagnoses for patients with rare diseases, and advancing research on genetic contributions to health and disease. Of particular interest are genomics- based screening programs, which will, in this publication, be clinical screening programs that examine genes or variants in unselected populations in order to identify individuals who are at an increased risk for a particular health concern (e.g., diseases, adverse drug outcomes) and who might benefit from clinical interventions. On November 1, 2017, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop to explore the challenges and opportunities associated with integrating genomics-based screening programs into health care systems. This workshop was developed as a way to explore the challenges and opportunities associated with integrating genomics-based programs in health care systems in the areas of evidence collection, sustainability, data sharing, infrastructure, and equity of access. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Evidence Considerations for Integrating Genomics-Based Programs into Health Care Systems 3 Financial Considerations for Implementing Genomics-Based Screening Programs 4 Exploring Approaches to Optimize Data Sharing Among Early Implementers of Genomics-Based Programs 5 Understanding Participant Needs and Preferences and Improving Diversity and Equity 6 Improving Health Through the Integration of Genomics-Based Programs: Potential Next Steps References Appendix A: Workshop Agenda Appendix B: Speaker Biographies Appendix C: Statement of Task Appendix D: Registered Attendees

Regenerative medicine products, which are intended to repair or replace damaged cells or tissues in the body, include a range of therapeutic approaches such as cell- and gene-based therapies, engineered tissues, and non-biologic constructs. The current approach to characterizing the quality of a regenerative medicine product and the manufacturing process often involves measuring as many endpoints as possible, but this approach has proved to be inadequate and unsustainable. The Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine convened experts across disciplines for a 2-day virtual public workshop to explore systems thinking approaches and how they may be applied to support the identification of relevant quality attributes that can help in the optimization of manufacturing and streamline regulatory processes for regenerative medicine. A broad array of stakeholders, including data scientists, physical scientists, industry researchers, regulatory officials, clinicians, and patient representatives, discussed new advances in data acquisition, data analysis and theoretical frameworks, and how systems approaches can be applied to the development of regenerative medicine products that can address the unmet needs of patients. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction 2 Introduction to Systems Thinking Concepts 3 Exploring the Challenges of Critical Quality Attributes: The Role of Systems Thinking 4 Challenges Associated with Data Collection, Aggregation, and Sharing 5 Challenges and Opportunities Associated with Systems-Level Analysis and Modeling 6 Addressing Regenerative Medicine Manufacturing and Supply Chain Challenges with Systems-Level Approaches 7 Exploring Issues of Workforce Development Related to Systems Thinking References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task

On February 26, 2020, the Board on Health Sciences Policy of the National Academies of Sciences, Engineering, and Medicine hosted a 1-day public workshop in Washington, DC, to examine current and emerging bioethical issues that might arise in the context of biomedical research and to consider research topics in bioethics that could benefit from further attention. The scope of bioethical issues in research is broad, but this workshop focused on issues related to the development and use of digital technologies, artificial intelligence, and machine learning in research and clinical practice; issues emerging as nontraditional approaches to health research become more widespread; the role of bioethics in addressing racial and structural inequalities in health; and enhancing the capacity and diversity of the bioethics workforce. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Ethically Leveraging Digital Technology for Health 3 Ethical Questions Concerning Nontraditional Approaches for Data Collection and Use 4 Understanding the Impact of Inequality on Health, Disease, and Who Participates in Research 5 Bioethics Research Workforce 6 Reflecting on the Workshop and Looking to the Future References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Recognizing the potential design complexities and ethical issues associated with clinical trials for gene therapies, the Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine held a 1-day workshop in Washington, DC, on November 13, 2019. Speakers at the workshop discussed patient recruitment and selection for gene-based clinical trials, explored how the safety of new therapies is assessed, reviewed the challenges involving dose escalation, and spoke about ethical issues such as informed consent and the role of clinicians in recommending trials as options to their patients. The workshop also included discussions of topics related to gene therapies in the context of other available and potentially curative treatments, such as bone marrow transplantation for hemoglobinopathies. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Developing First-in-Human Gene Therapy Clinical Trials 3 Understanding the Complexities of Patient Selection, Enrollment, and the Consent Process 4 Developing Endpoints for Gene Therapy Clinical Trials 5 Integrating Gene-Based Therapies into Clinical Practice: Exploring Long-Term Clinical Follow-Up of Patients 6 Reflections on the Workshop and Potential Opportunities for Next Steps References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

On June 26, 2017, the Forum on Regenerative Medicine hosted a public workshop in Washington, DC, titled Navigating the Manufacturing Process and Ensuring the Quality of Regenerative Medicine Therapies in order to examine and discuss the challenges, opportunities, and best practices associated with defining and measuring the quality of cell and tissue products and raw materials in the research and manufacturing of regenerative medicine therapies. The goal of the workshop was to learn from existing examples of the manufacturing of early-generation regenerative medicine products and to address how progress could be made in identifying and measuring critical quality attributes. The workshop also addressed the challenges of designing and adhering to standards as a way of helping those who are working to scale up processes and techniques from a research laboratory to the manufacturing environment. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Transitioning from Discovery and Development to Manufacturing 3 Identifying and Measuring Critical Quality Attributes 4 Designing Technologies to Meet the Manufacturing Needs of New Regenerative Medicine Therapies 5 Considerations for Improving and Regulating Regenerative Medicine Products 6 Potential Next Steps for Supporting the Development, Manufacture, and Regulation of Regenerative Medicine Therapies References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees